tbuckley/cabot-search huggingface dataset:
Orally Administrable Aggregation‐Induced Emission‐Based Bionic Probe for Imaging and Ameliorating Dextran Sulfate Sodium‐Induced Inflammatory Bowel Diseases
Authors: Wenyuan Wang, Ya Wu, Yihui Wang, Rui Wang, Cheng Deng, Luyang Yi, Lufang Wang, Mengrong He, Wuqi Zhou, Yuji Xie, Qiaofeng Jin, Yihan Chen, Tang Gao, Li Zhang, Mingxing Xie
Journal: Advanced Healthcare Materials (2022)

As macrophage infiltration is significantly related to the progression of inflammatory bowel disease (IBD), monitoring the macrophages is a valuable strategy for IBD diagnosis. However, owing to the harsh physiological environment of the gastrointestinal tract and enzymatic degradation, the development of orally administrable imaging probes for tracking macrophages remains a considerable challenge. Accordingly, herein, an orally administrable aggregation-induced emission biomimetic probe (HBTTPIP/β-glucan particles [GPs]) is developed for tracing macrophages; HBTTPIP/GPs can diagnose and alleviate dextran sulfate sodium (DSS)-induced colonic inflammation and self-report the treatment efficiency. The fluorophore HBTTPIP can effectively aggregate in GPs, restricting intramolecular rotation and activating the fluorescence of HBTTPIP. After being orally administrated, HBTTPIP/GPs are phagocytosed by intestinal macrophages, which then migrate to colonic lesions, enabling non-invasive monitoring of the severity of IBD via in vivo fluorescence imaging. Notably, oral HBTTPIP/GPs ameliorate DSS-induced IBD by inhibiting the expressions of pro-inflammatory factors and improving colonic mucosal barrier function. Furthermore, these HBTTPIP/GPs realize self-feedback of the therapeutic effects of GPs on DSS-induced colitis. The oral biomimetic probe HBTTPIP/GPs reported herein provide a novel theranostic platform for IBD, integrating non-invasive diagnosis of IBD in situ and the corresponding treatment.
A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets
Authors: Lin Wang, Jangham Jung, Husam Babikir, Karin Shamardani, Saket Jain, Xi Feng, Nalin Gupta, Susanna Rosi, Susan Chang, David Raleigh, David Solomon, Joanna J. Phillips, Aaron A. Diaz
Journal: Nature Cancer (2022)

Recent longitudinal studies of glioblastoma (GBM) have demonstrated a lack of apparent selection pressure for specific DNA mutations in recurrent disease. Single-cell lineage tracing has shown that GBM cells possess a high degree of plasticity. Together this suggests that phenotype switching, as opposed to genetic evolution, may be the escape mechanism that explains the failure of precision therapies to date. We profiled 86 primary-recurrent patient-matched paired GBM specimens with single-nucleus RNA, single-cell open-chromatin, DNA and spatial transcriptomic/proteomic assays. We found that recurrent GBMs are characterized by a shift to a mesenchymal phenotype. We show that the mesenchymal state is mediated by activator protein 1. Increased T-cell abundance at recurrence was prognostic and correlated with hypermutation status. We identified tumor-supportive networks of paracrine and autocrine signals between GBM cells, nonmalignant neuroglia and immune cells. We present cell-intrinsic and cell-extrinsic targets and a single-cell multiomics atlas of GBM under therapy.
Cholesteryl Ester Transfer Protein Inhibitors and Access to the Retina in Age-Related Macular Degeneration
Authors: Christine A. Curcio, Mark Johnson
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Promotion of Women's Surgical Training and Professional Expectations in Academic Surgery
Authors: Yi-Min Gu, Si-Mian Lyu, Long-Qi Chen
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Lentiviral Gene Therapy for Artemis-Deficient SCID
Authors: Morton J. Cowan, Jason Yu, Janelle Facchino, Carol Fraser-Browne, Ukina Sanford, Misako Kawahara, Jasmeen Dara, Janel Long-Boyle, Jess Oh, Wendy Chan, Shivali Chag, Lori Broderick, Deepak Chellapandian, Hélène Decaluwe, Catherine Golski, Diana Hu, Caroline Y. Kuo, Holly K. Miller, Aleksandra Petrovic, Robert Currier, Joan F. Hilton, Divya Punwani, Christopher C. Dvorak, Harry L. Malech, R. Scott McIvor, Jennifer M. Puck
Journal: New England Journal of Medicine (2022)

The DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in DCLRE1C, which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation.We carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing DCLRE1C, in 10 infants with newly diagnosed ART-SCID. We followed them for a median of 31.2 months.Marrow harvest, busulfan conditioning, and lentiviral-transduced CD34+ cell infusion produced the expected grade 3 or 4 adverse events. All the procedures met prespecified criteria for feasibility at 42 days after infusion. Gene-marked T cells were detected at 6 to 16 weeks after infusion in all the patients. Five of 6 patients who were followed for at least 24 months had T-cell immune reconstitution at a median of 12 months. The diversity of T-cell receptor β chains normalized by 6 to 12 months. Four patients who were followed for at least 24 months had sufficient B-cell numbers, IgM concentration, or IgM isohemagglutinin titers to permit discontinuation of IgG infusions. Three of these 4 patients had normal immunization responses, and the fourth has started immunizations. Vector insertion sites showed no evidence of clonal expansion. One patient who presented with cytomegalovirus infection received a second infusion of gene-corrected cells to achieve T-cell immunity sufficient for viral clearance. Autoimmune hemolytic anemia developed in 4 patients 4 to 11 months after infusion; this condition resolved after reconstitution of T-cell immunity. All 10 patients were healthy at the time of this report.Infusion of lentiviral gene-corrected autologous CD34+ cells, preceded by pharmacologically targeted low-exposure busulfan, in infants with newly diagnosed ART-SCID resulted in genetically corrected and functional T and B cells. (Funded by the California Institute for Regenerative Medicine and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03538899.).
Science and ART—Cardiovascular Disease Risk Assessment in HIV
Authors: Matthew J. Feinstein
Journal: JAMA Cardiology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura
Authors: Lars M. Asmis, Andreas Serra, Alexander Krafft, Abraham Licht, Elke Leisinger, Jana Henschkowski-Serra, Michael T. Ganter, Steffen Hauptmann, Marianne Tinguely, Johanna A. Kremer Hovinga
Journal: New England Journal of Medicine (2022)

A 27-year-old patient with a history of severe obstetrical complications and arterial thrombosis received a diagnosis of hereditary thrombotic thrombocytopenic purpura (TTP) due to severe ADAMTS13 deficiency when she presented with an acute episode in the 30th week of her second pregnancy. When the acute episode of hereditary TTP became plasma-refractory and fetal death was imminent, weekly injections of recombinant ADAMTS13 at a dose of 40 U per kilogram of body weight were initiated. The patient's platelet count normalized, and the growth of the fetus stabilized. At 37 weeks 1 day of gestation, a small-for-gestational-age boy was delivered by cesarean section. At the time of this report, the patient and her son were well, and she continued to receive injections of recombinant ADAMTS13 every 2 weeks. (Funded by the Swiss National Science Foundation.).
Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis
Authors: Evan S. Dellon, Marc E. Rothenberg, Margaret H. Collins, Ikuo Hirano, Mirna Chehade, Albert J. Bredenoord, Alfredo J. Lucendo, Jonathan M. Spergel, Seema Aceves, Xian Sun, Matthew P. Kosloski, Mohamed A. Kamal, Jennifer D. Hamilton, Bethany Beazley, Eilish McCann, Kiran Patel, Leda P. Mannent, Elizabeth Laws, Bolanle Akinlade, Nikhil Amin, Wei Keat Lim, Matthew F. Wipperman, Marcella Ruddy, Naimish Patel, David R. Weinreich, George D. Yancopoulos, Brad Shumel, Jennifer Maloney, Angeliki Giannelou, Arsalan Shabbir
Journal: New England Journal of Medicine (2022)

Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis.
Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity
Authors: Yaling Hu, Kelei Cao, Fang Wang, Weiying Wu, Weihao Mai, Liyao Qiu, Yuxiang Luo, Woo-ping Ge, Binggui Sun, Ligen Shi, Junming Zhu, Jianmin Zhang, Zhiying Wu, Yicheng Xie, Shumin Duan, Zhihua Gao
Journal: Nature Metabolism (2022)

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about the metabolic determinants in microglia. By mining large datasets and generating transgenic tools, here we show that hexokinase 2 (HK2), the most active isozyme associated with mitochondrial membrane, is selectively expressed in microglia in the brain. Genetic ablation of HK2 reduced microglial glycolytic flux and energy production, suppressed microglial repopulation, and attenuated microglial surveillance and damage-triggered migration in male mice. HK2 elevation is prominent in immune-challenged or disease-associated microglia. In ischaemic stroke models, however, HK2 deletion promoted neuroinflammation and potentiated cerebral damages. The enhanced inflammatory responses after HK2 ablation in microglia are associated with aberrant mitochondrial function and reactive oxygen species accumulation. Our study demonstrates that HK2 gates both glycolytic flux and mitochondrial activity to shape microglial functions, changes of which contribute to metabolic abnormalities and maladaptive inflammation in brain diseases. Hu et al. study the role of hexokinase 2 in microglial metabolism and function, and show its dual role under physiological and pathological conditions in a mouse model of stroke-induced neuroinflammation
Calling Out Disparities in Pancreatic Cancer Care
Authors: Michael A. Mederos, O. Joe Hines
Journal: JAMA Surgery (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Biologics in Eosinophilic Esophagitis — Ready for Prime Time?
Authors: Alex Straumann
Journal: New England Journal of Medicine (2022)

Eosinophilic esophagitis is an immune-mediated, chronic, inflammatory disease of the esophagus that was first recognized as a distinct entity less than three decades ago.1 The immunopathogenesis of the disease is characterized by type 2 helper T (Th2)–cell inflammation involving T cells, eosinophils, mast cells, and the cytokines interleukin-4, interleukin-5, interleukin-13, and thymic stromal lymphopoietin.2 These cells and mediators are potential targets for antiinflammatory medications. The prevalence of eosinophilic esophagitis has increased rapidly. In Western countries, the disease currently affects approximately 1 in 3000 persons.3 The most common symptom of eosinophilic esophagitis in adults is dysphagia with solid food intake, often . . .
A researcher’s guide to preclinical mouse NASH models
Authors: Suchira Gallage, Jose Efren Barragan Avila, Pierluigi Ramadori, Enrico Focaccia, Mohammad Rahbari, Adnan Ali, Nisar P. Malek, Quentin M. Anstee, Mathias Heikenwalder
Journal: Nature Metabolism (2022)
CD137 (4-1BB)-Based Cancer Immunotherapy on Its 25th Anniversary
Authors: Ignacio Melero, Miguel F. Sanmamed, Javier Glez-Vaz, Carlos Luri-Rey, Jun Wang, Lieping Chen
Journal: Cancer Discovery (2022)

Twenty-five years ago, we reported that agonist anti-CD137 monoclonal antibodies eradicated transplanted mouse tumors because of enhanced CD8+ T-cell antitumor immunity. Mouse models indicated that anti-CD137 agonist antibodies synergized with various other therapies. In the clinic, the agonist antibody urelumab showed evidence for single-agent activity against melanoma and non-Hodgkin lymphoma but caused severe liver inflammation in a fraction of the patients. CD137's signaling domain is included in approved chimeric antigen receptors conferring persistence and efficacy. A new wave of CD137 agonists targeting tumors, mainly based on bispecific constructs, are in early-phase trials and are showing promising safety and clinical activity. CD137 (4-1BB) is a costimulatory receptor of T and natural killer lymphocytes whose activity can be exploited in cancer immunotherapy strategies as discovered 25 years ago. Following initial attempts that met unacceptable toxicity, new waves of constructs acting agonistically on CD137 are being developed in patients, offering signs of clinical and pharmacodynamic activity with tolerable safety profiles.
Surgical Revascularization — Best for Limb Ischemia?
Authors: Jonathan Golledge
Journal: New England Journal of Medicine (2022)

In 2015, approximately 237 million people worldwide had been diagnosed with peripheral arterial disease, an increase of 17% from 2010.1 Peripheral arterial disease causes ischemia in the affected leg, which may lead to pain, impaired walking, gangrene, and ulceration and is associated with a high risk of major adverse cardiovascular events.2 The disease is managed medically by treating modifiable factors to reduce the risk of major adverse cardiovascular events.2 Chronic limb-threatening ischemia, the most advanced stage of peripheral arterial disease, may result in amputation if the ischemia is not resolved. The prevalence of chronic limb-threatening ischemia is 15% among Medicare . . .
A Ubiquitination Cascade Regulating the Integrated Stress Response and Survival in Carcinomas
Authors: Lisa D. Cervia, Tsukasa Shibue, Ashir A. Borah, Benjamin Gaeta, Linh He, Lisa Leung, Naomi Li, Sydney M. Moyer, Brian H. Shim, Nancy Dumont, Alfredo Gonzalez, Nolan R. Bick, Mariya Kazachkova, Joshua M. Dempster, John Michael Krill-Burger, Federica Piccioni, Namrata D. Udeshi, Meagan E. Olive, Steven A. Carr, David E. Root, James M. McFarland, Francisca Vazquez, William C. Hahn
Journal: Cancer Discovery (2022)

Abstract Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4 is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization of the heme-regulated inhibitor, a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. Significance: We describe the identification of a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This provides a novel insight on the regulation of ISR and exposes a therapeutic opportunity to selectively eliminate these cancer cells. See related commentary Leli and Koumenis, p. 535. This article is highlighted in the In This Issue feature, p. 517
Banking on virus-specific T cells to fulfill the need for off-the-shelf cell therapies
Authors: David H. Quach, Premal Lulla, Cliona M. Rooney
Journal: Blood (2022)

Adoptively transferred virus-specific T cells (VSTs) have shown remarkable safety and efficacy for the treatment of virus-associated diseases and malignancies in hematopoietic stem cell transplant (HSCT) recipients, for whom VSTs are derived from the HSCT donor. Autologous VSTs have also shown promise for the treatment of virus-driven malignancies outside the HSCT setting. In both cases, VSTs are manufactured as patient-specific products, and the time required for procurement, manufacture, and release testing precludes their use in acutely ill patients. Further, Good Manufacturing Practices-compliant products are expensive, and failures are common in virus-naive HSCT donors and patient-derived VSTs that are rendered anergic by immunosuppressive tumors. Hence, highly characterized, banked VSTs (B-VSTs) that can be used for multiple unrelated recipients are highly desirable. The major challenges facing B-VSTs result from the inevitable mismatches in the highly polymorphic and immunogenic human leukocyte antigens (HLA) that present internally processed antigens to the T-cell receptor, leading to the requirement for partial HLA matching between the B-VST and recipient. HLA mismatches lead to rapid rejection of allogeneic T-cell products and graft-versus-host disease induced by alloreactive T cells in the infusion product. Here, we summarize the clinical outcomes to date of trials of B-VSTs used for the treatment of viral infections and malignancies and their potential as a platform for chimeric antigen receptors targeting nonviral tumors. We will highlight the properties of VSTs that make them attractive off-the-shelf cell therapies, as well as the challenges that must be overcome before they can become mainstream.